In order to effect remission and healing of the indication of interest by effectively expressing pharmacological effect of an active ingredient contained in a pharmaceutical preparation, it is needless to say that appropriate dosage form and formulation of the pharmaceutical preparation must be selected depending not only on pharmacological properties of the active ingredient but also on its physicochemical properties and the kind and disease state of the indication of interest.
However, it often occurs that a developed medical compound selected based on-its excellent pharmacological effects is sparingly soluble in water despite of the expectation of fast-acting property in its indications.
Since sparingly soluble medicaments are also low in solubility in the digestive tracts, it is general that not only their absorption from the digestive tracts is poor but also their fast-acting property cannot be expected. In addition, in the case of a medicament which becomes sparingly soluble depending on pH, its dissolution property is affected by pH in the digestive tracts and meals of a patient, so that not only its bioavailability after administration is varied but also its fast-acting property cannot be expected in some cases.
In consequence, it is still an important techinical problem to design pharmaceutical preparations to solubilize sparingly soluble medicaments by certain means and to give rapidly disintegrable property, in expectation of attaining fast-acting property of the sparingly soluble medicaments.
Known processes for improving solubility and absorption of a sparingly soluble medicament include a process of finely dividing the medicament, a process for forming a solid dispersion, and the like. Among them, the process for forming a solid dispersion is considered to be generally usable in practice for the improvement of solubility and absorption of a sparingly soluble medicament (cf. an examined Japanese patent publication 59-48810 corresponding to U.S. Pat. No. 4,673,564).
The process for forming a solid dispersion using a polymer base to carry a sparingly soluble medicament is suited for a composition for sustained release preparation. It is however accompanied with the disadvantage that the polymer base formed into a solid dispersion does not contribute to the disintegration at all so that a disintegrating rate of the preparation in the body liquid is slow, which delays the dissolution of the medicament and therefore fast-acting property cannot be expected.
Also under investigation is a process for improving the absorption of a sparingly soluble medicament hold in a solid dispersion and the disintegration of the preparation. Examples thereof include compression molding obtained by granulating a mixture of a sparingly soluble medicament and a specific polymer such as polyvinyl pyrrolidone by fluidized bed granulation method, and a compression molding obtained by granulating a mixture obtained by compounding a sparingly soluble medicament, one or more components selected from the group consisting of PVP, urea, citric acid, mannitol, succinic acid, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and amino acid, and one or more components selected from the group consisting of a surfactant, polyethylene glycol, propylene glycol, glycerol, glycerol fatty acid ester and plant oil by fluidized bed granulation method (cf. an unexamined published Japanese patent application 56-110612). However, there is room for improvement in the above method, particularly, in disintegrable effects. It is desired to establish a formulation technique generally used in practice, for example, by only mixing the components and then compression molding the resultant mixture, without employing the fluidized bed granulation method.